JPH083109A - Production of 4-alkoxy-3,5,6-trifluorophthalic acid and 3-alkoxy-2,4,5-trifluorobenzoic acid - Google Patents

Abstract

PURPOSE: To provide a simplified method for producing the subject compounds useful as important intermediates for producing antibacterial agents having high activities, wherein the method does not have the defects of conventional techniques.

CONSTITUTION: This production method comprises allowing tetrafluorophthalic acid or tetrafluorophthalic acid anhydride to react with an alcohol of the formula; ROH (R is a 1-5C alkyl, 3-5C cycloalkyl or aralkyl group which may be monofluorinated or polyfluorinated) and a water-soluble base at 25-150°C, especially 60-100°C, in water, separating a produced 4-alkoxy-3,5,6-trifluorophthalic acid of formula I, optionally subjecting the compound of the formula I to a decarboxylation reaction in the presence of a basic solvent, if desired, in an inactive solvent at a temperature of 70-180°C, especially 100-150°C, and subsequently separating a produced 3-alkoxy-2,4,5-trifluorobenzoic acid of formula II.

COPYRIGHT: (C)1996,JPO

Description

Detailed Description of the Invention

[0001]

The present invention relates to 4-alkoxy-3,
5,6-trifluorophthalic acid and, if desired, 3-
It relates to a new and advantageous process for the production of alkoxy-2,4,5-trifluorobenzoic acid.

[0002]

BACKGROUND OF THE INVENTION 4-Alkoxy-3,5,6-trifluorophthalic acid and 3-alkoxy-2,4,5-trifluorobenzoic acid are both new and active from the fluoroquinolonecarboxylic acid family. It is an important intermediate for producing a high antibacterial agent (Japanese Patent Application Publication No. 297,366, European Patent Application Publication A4).
43498, European Patent Application Publication A230295.
No., European Patent Application Publication A241206 and Japanese Patent Application Publication No. 316,757).

4-Alkoxy-3,5,6-trifluorophthalic acid is generally obtained by the only synthetic process which is complicated and therefore economically disadvantageous. That is, 4-alkoxy-3,5,6-trifluorophthalic acid is obtained by the following method (report by Ishikawa et al., Pages 200 to 202 of Journal of Chemical Society of Japan-1 (1976) and European Patent Application Publication A271275. No.). : Tetrafluorophthalic acid is reacted with methanol to obtain the corresponding dimethyl tetrafluorophthalate, then the fluorine atom at the 4-position is substituted with a methoxy group, and 4-methoxy-
Obtain dimethyl 3,5,6-trifluorophthalate. Next, this dimethyl 4-methoxy-3,5,6-trifluorophthalate was hydrolyzed to give 4-methoxy-3,5,6-
Trifluorophthalic acid is obtained. 4 if you want
3-methoxy-2,4, by decarboxylating -methoxy-3,5,6-trifluorophthalic acid
5-Trifluorobenzoic acid can be obtained. This is shown in Reaction Formula A below. Reaction formula A

[0004]

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Technically possible 3-methoxy-2,4,5
-Trifluorobenzoic acid, 3-ethoxy-2,4,5-
Trifluorobenzoic acid, 3-propoxy-2,4,5-
Other known methods for producing trifluorobenzoic acid and 3-butoxy-2,4,5-trifluorobenzoic acid include 3-hydroxy-
It is carried out via 2,4,5-trifluorobenzoic acid, and the hydroxyl group at the 3 position must be selectively alkylated (see Japanese Patent Application Publication No. 268662). 3-hydroxy-2,4
5-Trifluorobenzoic acid can be prepared according to European patent application publication A 271275, the details of which are given below.

By hydrolyzing tetrafluorophthalic acid in an alkaline aqueous solution and substituting the fluorine atom at the 4-position with a hydroxyl group, 4-hydroxy-3,5,5 is obtained.
6-Trifluorophthalic acid is obtained. Then, 4-hydroxy-3,5,6-trifluorophthalic acid is decarboxylated to give 3-hydroxy-2,4,5-trifluorobenzoic acid. The corresponding 3-alkoxy-
Alkylating agent of 3-hydroxy-2,4,5-trifluorobenzoic acid to obtain 2,4,5-trifluorobenzoic acid, for example 3-methoxy-2,4,5-trifluorobenzoic acid , For example dimethylsulfate.

According to this method, for the decarboxylation reaction in acidic aqueous medium, 4-hydroxy-3,
If 4-alkoxy-3,5,6-trifluorophthalic acid is used instead of 5,6-trifluorophthalic acid, the formation of 3-alkoxy-2,4,5-trifluorobenzoic acid is traced. Or none at all. This is because
In this case, it is ether decomposition that occurs simultaneously under the conditions of decarboxylation of 4-alkoxy-3,5,6-trifluorophthalic acid, and in each case 3-hydroxy-2,4,5-trifluoro This produces benzoic acid but not the corresponding 3-alkoxy-2,4,5-trifluorobenzoic acid. (See European Patent Application Publication A271275). The above-mentioned synthesis method is shown in the following reaction formula B. Reaction formula B

[0008]

[Chemical 4]

Compared to the method shown in reaction formula B, the method shown in reaction formula A also directly gives 4-alkoxy-3,5,6-trifluorophthalic acid, but its reaction step Difficult due to the large number of Furthermore, from the viewpoint of reaction stoichiometry, 4-alkoxy-3,5,6-trifluorophthalic acid or 3-alkoxy-2,4,5 produced is
-Requires 3 moles or more of alcohol per mole of trifluorobenzoic acid. More than 2 moles of alcohol are needed to produce the corresponding diester from tetrafluorophthalic acid. The two ester groups are merely protective groups and are subsequently removed by hydrolysis with the removal of alcohol. This is an additional loss in view of the inaccessible valuable alcohol, since subsequent hydrolysis of the ester group synthesized from the valuable alcohol is not economical. Taking into account the attachment of the alkoxy groups, the alkylating agents which are necessary for the synthesis and which contain the corresponding alkyl groups which are important for obtaining the active substance, are obtained only in a strictly limited range and are therefore shown in Scheme B. It can be said that the method described above has relatively little variability. Furthermore, the handling of alkylating agents such as alkyl halides or dialkyl sulphates is very problematic as the alkylating agents are very toxic.

[0010]

SUMMARY OF THE INVENTION Therefore, the object of the present invention is not only 4-alkoxy-3,5,6-trifluorophthalic acid, but also 3-alkoxy-2,4,5 if desired.
-A method of producing trifluorobenzoic acid, which is simplified as compared to the prior art and does not suffer from the disadvantages mentioned above,
Another object is to provide a manufacturing method that can be used as widely as possible.

[0011]

[Means for Solving the Problems] This problem is solved by the following chemical formula (5):

[0012]

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[In the formula, R is an alkyl group having 1 to 5 carbon atoms which may be monofluorinated or polyfluorinated, and 3 to 3 in a ring which may be monofluorinated or polyfluorinated. It is a cycloalkyl group having 5 carbon atoms or an araliphatic group which may be monofluorinated or polyfluorinated. ] 4-alkoxy-3,5,6-trifluorophthalic acid represented by the following chemical formula (6)

[0014]

[Chemical 6]

This is achieved by a method for producing 3-alkoxy-2,4,5-trifluorobenzoic acid represented by the formula: wherein R is defined as in the above chemical formula (5). In this method, tetrafluorophthalic acid or tetrafluorophthalic anhydride is reacted with an alcohol represented by the general formula ROH in which R is defined in the above general formula and a water-soluble base in water at elevated temperature, 4-alkoxy-
The 3,5,6-trifluorophthalic acid is isolated and the 4-alkoxy-3,5,6-trifluorophthalic acid, if desired, 70% in the presence of a basic solvent and, if desired, an inert solvent.
To 180 ° C to decarboxylate and separate the resulting 3-alkoxy-2,4,5-trifluorobenzoic acid.

The basic reaction process of the present invention can be understood from the following reaction formula C.

[0017]

[Chemical 7]

Reaction Scheme C As will be readily apparent by comparison with the reaction schemes of Reaction Schemes A and B, the process according to the invention is substantially simpler than the prior art. Further, the present invention can be widely applied because a wide variety of alcohols can be preferably used in the first step of the reaction, that is, in substituting the fluorine atom at the 4-position with an alkoxy group. Furthermore, only 1 mol of alcohol is consumed for producing 1 mol of 4-alkoxy-3,5,6-trifluorophthalic acid or 3-alkoxy-2,4,5-trifluorobenzoic acid, respectively. Only. Surprisingly, it is not necessary to protect the two carboxyl groups of tetrafluorophthalic acid from esterification. The reaction proceeds with high selectivity and yields high yields of 4-alkoxy-3,5,6-trifluorophthalic acid. Further, the present invention provides a second step of the reaction, namely 4-alkoxy-3,5,6 for obtaining 3-alkoxy-2,4,5-trifluorobenzoic acid.
High yields are also guaranteed in the decarboxylation reaction of trifluorophthalic acid.

A further surprising feature is the formation of by-products, in particular the ether decomposition which accompanies the formation of 3-hydroxy-2,4,5-trifluorobenzoic acid is completely avoided.

Suitable alcohols for reaction with tetrafluorophthalic acid or tetrafluorophthalic anhydride are straight-chain or branched aliphatic alcohols, cycloaliphatic alcohols or araliphatic alcohols. The alcohol represented by the general formula ROH used in the reaction is a primary or secondary alcohol, particularly a primary alcohol.

Examples of the alcohol represented by the general formula ROH include methanol, ethanol, n-propanol,
n-butanol, n-pentanol, cyclopropanol, hydroxymethylcyclopropane, fluorinated methanol, difluorinated methanol, trifluorinated methanol, monofluorinated ethanol, difluorinated ethanol, trifluorinated ethanol, monofluorinated propanol , Butanol monofluoride, cyclopropanol monofluoride, cyclopropanol difluoride, benzyl alcohol, 4-fluorobenzyl alcohol or phenylethanol, but especially methanol, ethanol, cyclopropanol, n-propanol, fluorinated methanol, difluoride. Preferred are methanol fluoride, methanol trifluoride, ethanol monofluoride, butanol monofluoride, benzyl alcohol, and 4-fluorobenzyl alcohol.

To carry out the reaction, from 1 mol of tetrafluorophthalic acid or tetrafluorophthalic anhydride to 1 to 100 mol, in particular 20 to 80 mol, in particular 4
Preference is given to using 0 to 60 mol of alcohol.

The reaction is carried out in water in the presence of a water-soluble base. Water-soluble bases used include hydroxides, carbonates,
A phosphate, an alkali metal or alkaline earth metal hydrophosphate or a dihydrogen phosphate, or a mixture thereof. A particularly suitable water-soluble base is lithium hydroxide,
Includes lithium hydroxide hydrate, sodium hydroxide and potassium hydroxide.

Usually, 1 to 100 mol, in particular 1.1 to 10 mol, in particular 2 to 5 mol, of base are used per 1 mol of tetrafluorophthalic acid or tetrafluorophthalic anhydride.

The reaction is carried out in the presence of water. Tetrafluorophthalic acid or tetrafluorophthalic anhydride 1
Usually 1 to 1500 moles, especially 10 to 3 moles
00 mol, in particular 25 to 200 mol of water is used.

The reaction of tetrafluorophthalic acid or tetrafluorophthalic anhydride with an alcohol represented by the general formula ROH and a water-soluble base in water is carried out at an elevated temperature, usually at 25 to 150 ° C. . In most cases, this reaction is from 50 to 120 ° C., especially from 60 to 10
It has been found suitable to work at 0 ° C. However, it should be noted in this respect that the reaction temperature chosen is in a range based on the reactivity of the alcohol used in each case and other reaction conditions. The reaction temperature is adapted corresponding to the appropriate conditions.

At the end of the reaction, it is necessary to separate the required product from the resulting reaction mixture of the aqueous phase.
This is usually done by distilling off unreacted alcohol from the reaction mixture of the aqueous phase and adding 4-alkoxy- by adding acid and / or extraction from the reaction mixture of the aqueous phase.
It is carried out by separating 3,5,6-trifluorophthalic acid.

The reaction mixture of the unreacted alcohol-free aqueous phase is extracted with a water-insoluble organic or basic solvent. Suitable water-insoluble organic solvents are polar organic solvents such as dialkyl ethers or 1
Is an aliphatic carboxylic acid ester having 6 to 6 carbon atoms.

If it is desired to obtain 3-alkoxy-2,4,5-trifluorobenzoic acid by decarboxylating 4-alkoxy-3,5,6-trifluorophthalic acid, the unreacted alcohol It is advisable to extract the reaction mixture of the removed aqueous phase with a basic solvent and use this mixture for the next process. This procedure is particularly simple.

The basic solvent used is an organic base, for example a linear or branched aliphatic amine, mono- or polysubstituted pyrrole, pyrrolidone, imidazole, imidazolidinone, pyridine, pyrimidine, quinoline, isoquinoline, N. , N-dialkylcarboxamides or mixtures of these compounds, in particular trialkylamines having 4 to 20, preferably 6 to 14 carbon atoms in each alkyl group, mixtures of these trialkylamines, collidine, Quinoline, N-methylpyrrolidone,
N, N-dimethylacetamide, 1,3-dimethylimidazolidinone, or a mixture of these compounds.

In many cases it is advantageous to additionally use a solvent which is inert under the reaction conditions. The inert solvent used is an aromatic hydrocarbon, a mono- or polyhalogenated aromatic hydrocarbon or a mixture thereof. Suitable inert solvents are toluene, ethylbenzene, mesitylene, o-xylene, m-xylene, p-xylene, industrial grade xylene isomer mixtures, chlorobenzene, dichlorobenzene, trichlorobenzene, chlorotoluene, dichlorotoluene or these. It is a mixture.

As already mentioned above, the decarboxylation is carried out at 70 to 180 ° C. In many cases,
It has been found that decarboxylation can be carried out at 80 to 170 ° C, especially 100 to 150 ° C.

Following decarboxylation, the reaction mixture is extracted with an aqueous solution containing a base, the aqueous phase obtained is separated and acidified to give 3-alkoxy-2,4,5-trifluorobenzoic acid. Is precipitated and the precipitate is filtered off. The bases dissolved and used in water are alkali metal hydroxides and alkali metal carbonates, particularly lithium hydroxide, sodium hydroxide and potassium hydroxide. Following the separation of the aqueous phase, usually a mineral acid, such as hydrochloric acid, sulfuric acid or phosphoric acid, is used in a sufficient amount, i.e. sufficient to bring the pH to 0 to 3, in particular 1 to 2.5, The alkoxy-2,4,5-trifluorobenzoic acid is filtered.

[0034]

The following examples illustrate, but do not limit, the present invention. Example 1 Reaction with methanol 4.4 g of tetrafluorophthalic anhydride (20 mmo
l) was dissolved in 6 g of water and 30 g of methanol,
The solution is heated to 30 ° C. and colored yellow. 8.2 g (0.2 mol) of lithium hydroxide hydrate is added and the mixture is refluxed at 65 ° C. for 10 hours. Shortly thereafter, tetrafluorophthalic anhydride is detected by GC analysis.
30 g of water was added, and a mixture of unreacted methanol and water (3
9 g) are distilled off completely until the top temperature reaches 100 ° C. The mixture is then adjusted to pH 1 with 30% strength hydrochloric acid and the colorless precipitate obtained is suction filtered. Aqueous phase is 1,2-dichlorobenzene 20 each
g and 10 g of Hostarex A327 (mixture of various aliphatic trialkylamines carrying 6 to 14 carbon atoms in the alkyl group) twice. After this extraction, the organic acids detected by GC analysis are not contained in the aqueous phase. The extract is heated to 140 ° C. for 2 hours until the evolution of gas (decarboxylation reaction) has ended. After cooling, this phase is alkalized (pH ≧ 11) with aqueous sodium hydroxide solution and extracted several times with dichloromethane. Distill the remaining aqueous phase with H
Collect ostarex A327 and solvent. The aqueous phase is then acidified again (pH 1) and extracted twice with 20 g of methyl t-butyl ether (MTBE) each. The extract was dried over MgSO ₄ , filtered and the solvent removed on a rotary evaporator to give G
2.7 g of a pale yellow powder identified as methoxytrifluorobenzoic acid (GC purity> 95%) by C-MS (13.
1 mmol, equivalent to 66%) remains. This can be further purified by stirring with hot water (recrystallization). Example 2 Reaction with Methanol The procedure of Example 1 was followed, but instead of Hostarex A327, instead of MTBE20 three times each.
Extraction is carried out using g. The organic phase was dried over MgSO ₄ , filtered and the solvent removed to give a yellowish 4-methoxy-3,5,6-trifluorophthalic acid (G
Purity according to C> 90%) 3.8 g (15.2 mmol,
76%) is obtained. Example 3 Reaction with ethanol 4.4 g of tetrafluorophthalic anhydride (20 mmo
1) is dissolved in 3 g of water and 30 g of ethanol, 4.2 g of lithium hydroxide hydrate are added, the mixture is heated to reflux for 48 hours. Then 50 g of water are added and the ethanol / water mixture (31.9 g) is distilled off until the top temperature reaches 100 ° C. After adding 19 g of 30% hydrochloric acid to adjust the pH to 0.6, 20 g of 1,2-dichlorobenzene and 10 g of Hostarex A327 are added.
The mixture is extracted with a mixture of. The organic phase is M
Dry with gSO ₄ and heat to 140 ° C. for 1 hour until gas evolution (decarboxylation) is complete, then 2
The pH is adjusted to 14 with 12.1 g of 35% aqueous sodium hydroxide solution at 5 ° C. Mix the mixture 5 times, 3 times each
Extract with 0 g of dichloromethane and add 30% to the aqueous phase.
Adjust the pH to 0.7 by adding 9.4g of concentrated hydrochloric acid and MT
Extract with BE. The mixture was dried over MgSO ₄ , filtered and the solvent was separated off to give a yellowish 3-
Ethoxy-2,4,5-trifluorobenzoic acid (purity> 95% by GC) 3.4 g (15.5 mmol, 77)
% Equivalent) is obtained. 3-Ethoxy-2,4,5-trifluorobenzoic acid: MS: m / e (%): 99 (8.8), 119 (7.
8), 147 (6.5), 174 (5.1), 175
(98.2), 192 (100), 193 (6.2),
220 (23.4) Example 4 Reaction with ethanol Following the procedure of Example 3 and using 4-ethoxy- as shown in Example 2.
By separating 3,5,6-trifluorophthalic acid,
4-ethoxy-3,5,6-trifluorophthalic acid 4.
6 g (17.4 mmol, 87% equivalent) are obtained. 4-Ethoxy-3,5,6-trifluorophthalic acid MS: m / e (%): 78 (9.8), 98 (26.
3), 117 (29), 146 (71.4), 174
(100), 175 (5.9), 218 (70.6),
246 (25.5, (M-H 2 O) + Example 5 reaction water 7.6g of trifluoroethanol, lithium hydrate 2.1g hydroxide, trifluoroethanol 10 g, tetrafluorophthalic anhydride 2. The first reaction material consisting of 2 g (10 mmol) of the mixture was heated for 96 hours at 70 ° C. and the content of tetrafluorophthalic anhydride fell below 1% (GC). Fluoroethoxy-
1.4 g of 2,4,5-trifluorobenzoic acid (5.1 m
mol, corresponding to 51%). Example 6 Reaction with Trifluoroethanol Following the procedure of Example 5 but substituting the phthalic acid as shown in Example 2 instead of decarboxylation, 4-trifluoroethoxy-3,5, a pale yellow solid. 2.2 g (6.9 mmol, 69% equivalent) of 6-trifluorophthalic acid are obtained.

The solid Starstar A3 was then applied to this solid.
Decarboxylation is carried out by adding 27 (324) and heating according to the procedure shown in Example 5. 2,2,3,3-Tetrafluoropropanol reacts in a very similar way. 4-Trifluoroethoxy-3,5,6-trifluorophthalic acid: MS: m / e (%): 79 (14), 83 (7), 98.
(12), 117 (42), 129 (14), 145
(17), 146 (11), 157 (5), 159 (3
0), 228 (100), 229 (8), 256 (8)
9), 281 (13), 300 (M-H 2 O) +, 9
0), 301 (9) Example 7 Reaction with 4-fluorobenzyl alcohol 8.4 g (0.15 mol) of potassium hydroxide in 30 g of water
Dissolved in 6.6 g of tetrafluorophthalic anhydride (3 g
0 mmol) and 4-fluorobenzyl alcohol 30 g
(0.238 mol) is added. Mix at 100 ° C for 1
Heat for 2 hours, then follow the procedure given in Example 2. It is advantageous not to bring the pH below 3 by the extraction stage. 3. By this method (4-fluorobenzyloxy) trifluorobenzoic acid (purity 80-85%) 4.
2 g (14 mmol, 47% equivalent) are obtained.

Claims (18)

[Claims] 1. The following general formula (1): [In the formula, R represents an alkyl group having 1 to 5 carbon atoms which may be monofluorinated or polyfluorinated, 3 to 5 carbon atoms in a ring which may be monofluorinated or polyfluorinated. It is a cycloalkyl group having a carbon atom or an araliphatic group which may be monofluorinated or polyfluorinated. ] 4-alkoxy-3 represented by
5,6-trifluorophthalic acid or, if desired, the following general formula (2) A method for producing 3-alkoxy-2,4,5-trifluorobenzoic acid represented by the formula [wherein R is defined as in the above general formula (1)], wherein tetrafluorophthalic acid or tetrafluorophthalic acid is used. 4-Alkoxy-3,5 produced by reacting fluorophthalic anhydride with an alcohol represented by the general formula ROH in which R is defined by the above general formula and a water-soluble base in water at elevated temperature. , 6-Trifluorophthalic acid is separated and, if desired, 4-alkoxy-3,5,6-
Decarboxylation of trifluorophthalic acid in the presence of a basic solvent and, if desired, an inert solvent at 70 to 180 ° C. to separate the 3-alkoxy-2,4,5-trifluorobenzoic acid formed. The method for producing 4-alkoxy-3,5,6-trifluorophthalic acid and 3-alkoxy-2,4,5-trifluorobenzoic acid, which comprises: 2. The method according to claim 1, wherein the alcohol represented by the general formula ROH used is a primary alcohol. 3. The alcohol represented by the general formula ROH used is methanol, ethanol, n-propanol,
n-butanol, n-pentanol, cyclopropanol, hydroxymethylcyclopropane, fluorinated methanol, difluorinated methanol, trifluorinated methanol, monofluorinated ethanol, difluorinated ethanol, trifluorinated ethanol, monofluorinated propanol Or monofluorobutanol, monofluorocyclopropanol, difluorocyclopropanol, benzyl alcohol, 4-fluorobenzyl alcohol or phenylethanol.
The method described in. 4. The alcohol represented by the general formula ROH used is methanol, ethanol, cyclopropanol, n-propanol, fluorinated methanol, difluorinated methanol, trifluorinated methanol, monofluorinated ethanol,
The method according to any one of claims 1 to 3, which is butanol monofluoride, benzyl alcohol, or 4-fluorobenzyl alcohol. 5. 1 to 100 moles relative to 1 mole of tetrafluorophthalic acid or tetrafluorophthalic anhydride,
5. The process according to claim 1, wherein in particular 20 to 80 mol, in particular 40 to 60 mol, of alcohol are used. 6. An alkali metal or alkaline earth metal hydroxide, carbonate, phosphate, hydrogenated phosphate or dihydrogenated phosphate, or a mixture thereof is used as a water-soluble base. 6. The method according to any one of 5 to 5. 7. The method according to claim 1, wherein lithium hydroxide, lithium hydroxide hydrate, sodium hydroxide or potassium hydroxide is used as a water-soluble base. 8. 1 to 100 moles, in particular 1.1 to 10 moles, in particular 2 to 5 moles, of base are used per mole of tetrafluorophthalic acid or tetrafluorophthalic anhydride. The method according to any one of 1. 9. A method according to claim 1, wherein 1 to 1500 mol, in particular 10 to 300 mol, in particular 25 to 200 mol of water is used per 1 mol of tetrafluorophthalic acid or tetrafluorophthalic anhydride. The method according to item 1. 10. Tetrafluorophthalic acid or tetrafluorophthalic anhydride is added at 25 to 150 ° C., especially 5
10. The process according to claim 1, wherein the reaction with alcohol is carried out at 0 to 120.degree. C., especially at 60 to 100.degree. 11. Unreacted alcohol is removed from the reaction mixture of the aqueous phase by distillation to give 4-alkoxy-3,5,5.
A process according to any one of claims 1 to 10, wherein 6-trifluorophthalic acid is separated by addition of acid and / or extraction from the reaction mixture of the aqueous phase. 12. The reaction mixture of the aqueous phase is extracted with a water-insoluble organic solvent, in particular a dialkyl ether or an aliphatic carboxylic acid ester having 1 to 6 carbon atoms, or a basic solvent. One of
The method described in the section. 13. A linear or branched aliphatic amine, optionally mono- or polyalkyl-substituted pyrrole, pyrrolidone, imidazole, imidazolidinone, pyridine, pyrimidine, quinoline, isoquinoline, N, N.
13. A dialkylated carboxamide or a mixture of these compounds is used as basic solvent.
The method according to any one of claims 1 to 4. 14. A trialkylamine having 4 to 20 carbon atoms in each alkyl group, mixtures of these trialkylamines, collidine, quinoline, N-methylpyrrolidone, N, N-dimethylacetamide, 1,3- 14. The method according to any one of claims 1 to 13, wherein dimethylimidazolidinone or a mixture of these compounds is used as a basic solvent. 15. The process according to claim 1, wherein an aromatic hydrocarbon, a mono- or polyhalogenated aromatic hydrocarbon or a mixture thereof is used as an inert solvent. 16. Toluene, ethylbenzene, mesitylene, o-xylene, m-xylene, p-xylene, industrial quality xylene isomer mixture, chlorobenzene, dichlorobenzene, trichlorobenzene, chlorotoluene,
16. The method according to any one of claims 1 to 15, wherein dichlorotoluene or a mixture thereof is used as an inert solvent. 17. 80 to 170 ° C., in particular 100 to 1
The method according to any one of claims 1 to 16, wherein the decarboxylation reaction is carried out at 50 ° C. 18. After the decarboxylation reaction, the reaction mixture is extracted with a basic aqueous solution, the aqueous phase is separated and acidified to precipitate 3-alkoxy-2,4,5-trifluorobenzoic acid. The method according to any one of claims 1 to 17, wherein the precipitate is filtered and separated.